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eLetters

16 e-Letters

We agree with DiNicolantonio´s and O´Keefe´s hypothesis that a high intake of omega-6 vegetable oils may promote coronary heart disease (CHD).1 However, we think that the mechanism is not oxidation of LDL-cholesterol (LDL-C). It is a solidly documented but little-known fact that LDL partake in the immune system by adhering to and inactivating almost all types of microorganisms.2 As the LDL-covered microorganisms are oxidized after having been taken up by macrophages, we think that the oxidation of LDL is a secondary phenomenon. The crucial event is most likely, as explained in our papers,2,3 that complexes of LDL-covered microorganisms may aggregate, in particular in the presence of
hyperhomocysteinemia, because homocysteine thiolactone causes aggregation and precipitation of thiolated LDL. Because of the high extra-capillary tissue pressure, aggregates of such complexes may be trapped in vasa vasorum of the major arteries and result in ischemia of the arterial wall. The reason why omega-6 oils promote CHD may be that these oils may result in increased coagulation,4 which is a well-known risk factor for CHD, even among individuals with familial hypercholesterolemia.5

We agree with DiNicolantonio´s and O´Keefe´s hypothesis that a high intake of omega-6 vegetable oils may promote coronary heart disease (CHD).1 However, we think that the mechanism is not oxidation of LDL-cholesterol (LDL-C). It is a solidly documented but little-known fact that LDL partake in the immune system by adhering to and inactivating almost all types of microorganisms.2 As the LDL-covered microorganisms are oxidized after having been taken up by macrophages, we think that the oxidation of LDL is a secondary phenomenon. The crucial event is most likely, as explained in our papers,2,3 that complexes of LDL-covered microorganisms may aggregate, in particular in the presence of
hyperhomocysteinemia, because homocysteine thiolactone causes aggregation and precipitation of thiolated LDL. Because of the high extra-capillary tissue pressure, aggregates of such complexes may be trapped in vasa vasorum of the major arteries and result in ischemia of the arterial wall. The reason why omega-6 oils promote CHD may be that these oils may result in increased coagulation,4 which is a well-known risk factor for CHD, even among individuals with familial hypercholesterolemia.5

Clinical practice has been historically driven by evidence-based medicine. Properly sized randomized controlled trials have been the basis of accepting or rejecting research hypotheses, and clinical guidelines are developed based on data reported in such trials. Clinical research is not perfect. However, most clinical trials are conducted in a highly regulated environment and accepted for publication following a strict peer review process led by independent experts. While limitations exist in conducting and reporting clinical trials, investigators are judged at very high ethical and academic standards.

A blog posted on September 11, 2017[1] questioned the integrity of the data and ethical conduct of the investigators of this study published in Open Heart. Due to the respect I have for the editor and this journal, I am obliged to respond on behalf of the authors.

First, I did not receive ANY type of financial compensation as the principal investigator for this study. Second, no financial obligations or equity arrangements exist between the sponsor of the study, myself or my current Institution. Third, although all financial disclosures of all authors were properly disclosed to the journal at the time of submission, they were unfortunately not included in the final published article and therefore published subsequently as a correction[2]. Fourth, the objective of the study was to assess the 3-week healing properties of a surface-modified stent. The patient wi...

Clinical practice has been historically driven by evidence-based medicine. Properly sized randomized controlled trials have been the basis of accepting or rejecting research hypotheses, and clinical guidelines are developed based on data reported in such trials. Clinical research is not perfect. However, most clinical trials are conducted in a highly regulated environment and accepted for publication following a strict peer review process led by independent experts. While limitations exist in conducting and reporting clinical trials, investigators are judged at very high ethical and academic standards.

A blog posted on September 11, 2017[1] questioned the integrity of the data and ethical conduct of the investigators of this study published in Open Heart. Due to the respect I have for the editor and this journal, I am obliged to respond on behalf of the authors.

First, I did not receive ANY type of financial compensation as the principal investigator for this study. Second, no financial obligations or equity arrangements exist between the sponsor of the study, myself or my current Institution. Third, although all financial disclosures of all authors were properly disclosed to the journal at the time of submission, they were unfortunately not included in the final published article and therefore published subsequently as a correction[2]. Fourth, the objective of the study was to assess the 3-week healing properties of a surface-modified stent. The patient with pancreatitis mentioned in the article died from non-cardiovascular causes several months beyond the reported follow up period, which is why the patient was not included in the study results. Finally, the study was properly approved and conducted according to the recommendations and guidelines of local investigators, ethics committees and regulatory authorities.

As leaders in the medical community, we are bound by a strong code of ethics. Medical innovation thrives when there is collaboration among physicians, engineers, business people and funding sources. The innovation ecosystem, although far from perfect, has been responsible for the development of truly disruptive technologies that have made a real impact on humanity. Medical media outlets have a responsibility to ensure that all developments in the field, including successes and failures, are reported based on facts and in an accurate and professional fashion.

Lee et al in trying to define the accuracy of one method illustrate the huge weakness in echo vs MRI comparative data. First and foremost neither FAC or TAPSE correlated that well with RVEF ( FAC only slightly better) although statistically significant this difference is clinically of negligible importance. Secondly in assuming that MRI provides a gold standard for RVEF. As with echo there are strengths and weaknesses of MRI. On is the rather lower sensitivity to long axis abnormalities because ventricular volumes are usually defined using the short axis plane. So a reduced correlation between a purely long axis technique, a moderate correlation with a technique that has both long and short axis components and one which is defined using predominantly radial function is entirely to be expected. Long axis dysfunction is usually the first sign of ventricular deterioration with short axis hyperactivity to compensate - exactly the example cited post cardiac surgery. Finally in their conclusions they state that FAC provides a better guide to RV systolic function. This is not justified - what it does do is provide a slightly better estimate of RVEF -these two are not synonymous. So as there are no clinical correlates - prognosis, symptoms, exercise performance, hospitalisations , the comparison between the techniques tells us nothing we did not already know - all methods of defining systolic function are different - we have not answered which one is best.

DiNicolantonio and McCarty suggest that the inverse association between low cholesterol and mortality in elderly people reflects reverse causality; meaning that the low cholesterol is caused by the disorder being treated.1 One of their arguments is that those whose cholesterol decreases with increasing age die more frequently from cancer and other diseases, compared to those with low cholesterol prior to treatment. However, many studies have shown that low cholesterol may predispose to cancer2 as well as infectious diseases.3 In a previous paper2 we identified nine cohort studies including more than 140,000 individuals, in which cancer was inversely associated with cholesterol measured 10–30 years earlier, and where the association persisted after exclusion of cancer cases appearing during the first 4 years.
The authors claim that statin treatment does not increase the risk of cancer based on a meta-analysis of 27 randomised trials published by the Cholesterol Treatment Trialists’ (CTT) Collaborators. But very few statin trials have continued for more than five years, and most carcinogenic chemicals need more time to create cancer. In spite of that cancer appeared significantly more often in three statin trials (2). In two other trials, non-melanoma skin cancer appeared more often and with statistical significance if the figures from the two trials were calculated together (2). Since then the number of non-melanoma skin cancers has not been reported in any trial. Fu...

DiNicolantonio and McCarty suggest that the inverse association between low cholesterol and mortality in elderly people reflects reverse causality; meaning that the low cholesterol is caused by the disorder being treated.1 One of their arguments is that those whose cholesterol decreases with increasing age die more frequently from cancer and other diseases, compared to those with low cholesterol prior to treatment. However, many studies have shown that low cholesterol may predispose to cancer2 as well as infectious diseases.3 In a previous paper2 we identified nine cohort studies including more than 140,000 individuals, in which cancer was inversely associated with cholesterol measured 10–30 years earlier, and where the association persisted after exclusion of cancer cases appearing during the first 4 years.
The authors claim that statin treatment does not increase the risk of cancer based on a meta-analysis of 27 randomised trials published by the Cholesterol Treatment Trialists’ (CTT) Collaborators. But very few statin trials have continued for more than five years, and most carcinogenic chemicals need more time to create cancer. In spite of that cancer appeared significantly more often in three statin trials (2). In two other trials, non-melanoma skin cancer appeared more often and with statistical significance if the figures from the two trials were calculated together (2). Since then the number of non-melanoma skin cancers has not been reported in any trial. Furthermore, cancer has been associated with statin treatment in several cohort and case–control studies as well (2), and also in several animal experiments (2).
There is a massive documentation to support the claim that low LDL-C predisposes to infectious diseases (3). In a meta-analysis of 19 cohort studies that included 68,406 deaths, Jacobs et al. found an inverse association between cholesterol and mortality from respiratory and gastrointestinal diseases, most of which are due to infections (3). It is unlikely that these diseases caused low cholesterol because these associations persisted after the exclusion of deaths occurring during the first 5 years.
Additional support comes from a 15-year follow-up study of more than 120,000 individuals by Iribarren et al. They found a strong inverse association between cholesterol as determined initially, and the subsequent risk of being admitted to hospital due to an infectious disease (3). Obviously, a disease they had not yet achieved could not have caused their low cholesterol.
DiNicolantonio and McCarty believe that the most conclusive evidence disputing a causal relationship between low LDL-C and cancer is provided by Mendelian randomisation, according to which none of the genotypes linked to lower LDL-C are associated with higher cancer risk. But association does not mean causation. Other genes in the same individual may have opposite effects, and as pointed out by Burgess et al: ”Power, linkage disequilibrium, pleiotropy, canalization and population stratification have all been recognized as potential flaws in the Mendelian randomization approach”.5
They also suggest that a high plasma level of interleukin-6 (IL-6) lowers LDL-C and that high IL-6 is the real cause of increased mortality because it is associated with higher rates global mortality in the elderly. However, it is also associated with various infections as well,6,7 which could be another explanation. What is little known, although it has been documented again and again by at least a dozen research groups, is that LDL partakes in the immune system by adhering to and inactivating almost all kinds of microorganisms and their toxic products.8,9 It is therefore more likely that the low LDL-C is the culprit, rather than an elevated IL-6. Why low LDL-C causes cancer remains to be elucidated.

We read with great interest Kaura and colleagues’ evaluation of a multidisciplinary care team for hospital inpatients with infective endocarditis (IE) (1). The study provides further evidence for the effectiveness of a team-based approach to IE care – a model endorsed by both European (2) and American (3) guidelines. Despite limitations inherent in a before-and-after study design, it is clear that the IE team provides patients rapid access to cardiology, microbiology, and surgical care with coordination between services.

Notably absent from this multidisciplinary approach, however, is care for substance use disorders. We wish to draw readers’ attention to the 10% of study participants for whom injection drug use (IDU) was identified as a predisposing factor in their IE. We believe a coordinated IE team offers enormous potential to provide addictions care and harm reduction services for patients with IE who inject drugs.

Compared with people who do not inject drugs, people who inject drugs are far more likely to have recurrences and repeat hospitalizations for IE, and face increased mortality risk after a first episode of IE (4,5). Rates of hospitalization for IDU-associated IE also appear to be increasing (4,6–8).

Evidence-based interventions can be provided in-hospital to reduce both rates of injecting and harms associated with ongoing injection. These interventions include initiating opioid agonist therapies (e.g. methadone or buprenorphine) for opi...

We read with great interest Kaura and colleagues’ evaluation of a multidisciplinary care team for hospital inpatients with infective endocarditis (IE) (1). The study provides further evidence for the effectiveness of a team-based approach to IE care – a model endorsed by both European (2) and American (3) guidelines. Despite limitations inherent in a before-and-after study design, it is clear that the IE team provides patients rapid access to cardiology, microbiology, and surgical care with coordination between services.

Notably absent from this multidisciplinary approach, however, is care for substance use disorders. We wish to draw readers’ attention to the 10% of study participants for whom injection drug use (IDU) was identified as a predisposing factor in their IE. We believe a coordinated IE team offers enormous potential to provide addictions care and harm reduction services for patients with IE who inject drugs.

Compared with people who do not inject drugs, people who inject drugs are far more likely to have recurrences and repeat hospitalizations for IE, and face increased mortality risk after a first episode of IE (4,5). Rates of hospitalization for IDU-associated IE also appear to be increasing (4,6–8).

Hospital admissions for IDU-associated IE represent an opportunity for clinicians to reach patients who are less likely to seek medical attention, and for many patients may provide new motivation to engage in treatment for substance use disorders (16–23). Treatment of acute opioid withdrawal at the time of admission, managing the substance use disorder, and establishing a therapeutic alliance can help to improve adherence to medical management of IE and avoid unplanned discharges against medical advice that often result from active, untreated substance use disorders (10,13,16,18,19,24–31).

Unfortunately, inpatient treatment for IDU-associated IE often focuses on the infection and the medical sequelae without addressing the underlying substance use disorder (9,28,32–35). For example, in a recent study of patients treated for IDU-associated IE at a Boston hospital, only 8% had a plan for opioid agonist therapy at the time of discharge (32).

There are multiple reasons for this implementation gap (28,35). Most physicians do not feel competent in addictions care (36,37). Jurisdictions have different limitations on methadone or buprenorphine prescribing, and institutions may not have clear pathways to identify community-based clinicians to continue prescribing opioid agonist therapy following hospital discharge (38,39). In our institutions (which do not yet have multidisciplinary IE care teams), patients with IE may be admitted or discharged through internal medicine, cardiology, cardiac surgery, or critical care, with ad hoc coordination between those services along with infectious diseases or medical microbiology. Each service may feel that the substance use disorder underlying the IE, and the associated increased risks of recurrence and mortality, are not within their scope of practice and are not the responsibility of their particular discipline (34). Clearly reducing these risks is in the best interests of our patients and our communities – so whose responsibility will it be?

While the European and American endocarditis guidelines do not specify how addiction medicine could fit into multidisciplinary IE care teams, recommendations from the British Heart Valve Society specify that all patients with IE who inject drugs should be offered addictions care (40). National and international IE guidelines should consider injection drug use as an important co-morbidity to address as part of patient-centred IE care.

A coordinated, multidisciplinary care team responsible for all inpatients with IE represents an indispensable opportunity to integrate addiction medicine expertise and offer care for substance use disorders to every patient with IE who injects drugs. An IE team should help facilitate initiation of opioid agonist therapy and promote other harm reduction strategies during hospital admissions in order to reduce the heightened risks of early hospital discharges against medical advice, recurrent infective endocarditis, and mortality. This approach could prolong life and reduce suffering for our patients with IE who inject drugs.

The citizenry of India are especially sensitive to excessive linoleic
acid intake as noted by S. L. Malhotra in a research paper published back
in 1967. Excerpt: "Much evidence indicates that consumption of even small
quantities of unsaturated fatty acids decreases the liability to ischaemic
heart disease (Bronte-Stewart et al., 1956; Kinsell et al., 1952). This
hypothesis, too, does not find support in our data. The South...

The citizenry of India are especially sensitive to excessive linoleic
acid intake as noted by S. L. Malhotra in a research paper published back
in 1967. Excerpt: "Much evidence indicates that consumption of even small
quantities of unsaturated fatty acids decreases the liability to ischaemic
heart disease (Bronte-Stewart et al., 1956; Kinsell et al., 1952). This
hypothesis, too, does not find support in our data. The South Indians eat
largely seed oils containing as much as 45 per cent poly-unsaturated fatty
acids, whereas ghee and other milk fats eaten by the Punjabis contain only
2 per cent polyunsaturated fatty acids...A survey of the incidence of
acute myocardial infarction and the dietary behaviour in railway
populations in India showed that the disease was 7 times more common among
South Indians as compared with the Punjabis in the North, even though the
fat intake of Punjabis was 8-19 times more than that of South Indians, and
was chiefly of animal origin."[1]

In line with Malhotra's findings, here is an excerpt from a May 1,
2016 article published in the Times of India: "Clarified butter remained
India's culinary star for centuries till it was sidelined in the 1980s by
vegetable oils because of its high saturated fat. The new oils were
aggressively marketed as superior and heart-healthy. Of late, research has
shown that saturated fats have no link to obesity, heart disease or early
death."[2]

It's been noted that "No country has successfully reduced obesity
rates in 33 years."[3] Perhaps the time has come to develop a new health
paradigm. Obviously, the anti-saturated fat campaign has not been
particularly helpful.[4]

Conflict of Interest:

Dietary advice that reducing fat and saturated fat consumption will
reduce the risk of coronary heart disease was introduced in the UK in
1983. The authors of this systematic review and meta-analysis conclude
that evidence from randomised controlled trials, available at the time,
did not support that advice.

It is important to highlight that the review looks at the results of
just six relatively short-term ra...

Dietary advice that reducing fat and saturated fat consumption will
reduce the risk of coronary heart disease was introduced in the UK in
1983. The authors of this systematic review and meta-analysis conclude
that evidence from randomised controlled trials, available at the time,
did not support that advice.

It is important to highlight that the review looks at the results of
just six relatively short-term randomised controlled trials (RCTs), whose
limitations are acknowledged by the authors. In 1983, there was already
good evidence that saturated fats in the diet raise blood cholesterol and
that blood cholesterol was a modifiable risk factor for coronary heart
disease.

More evidence for the effects of saturated fat has accumulated since
1983. Government advice to limit saturated fat intake to no more than 11%
of total food energy in order to reduce the risk of cardiovascular disease
is based on long standing advice from the Committee on Medical Aspects of
Food Policy (COMA) and is endorsed by the Scientific Advisory Committee on
Nutrition (2008), which now provides the UK with independent advice on
nutrition. The advice is supported by a wealth of evidence and is in line
with more recent assessments made by the Institute of Medicine (2005),
World Health Organization (2008) and the European Food Safety Authority
(2010).

There is good evidence from randomised controlled trials (RCTs) to
demonstrate that saturated fat consumption influences cholesterol levels
and increases the risk of cardiovascular disease. For example, the RISCK
study, a 6 month trial that analysed results from 548 men and women, found
that total cholesterol and LDL cholesterol concentrations were
significantly lower after consumption of diets lower in saturated fat
compared to the control group (Jebb et al. 2010). Skeaff and Miller (2009)
conducted a meta-analysis of 16 trials modifying the amount of saturated
fat in the diet and found that, in studies which significantly lowered
serum cholesterol by replacing saturated fat with polyunsaturated fat,
both heart attacks and deaths from heart disease were significantly
reduced. More recently a Cochrane Collaboration systematic review (Hooper
et al. 2012) concluded that reducing saturated fat by reducing and/or
modifying dietary fat intakes lowered the risk of cardiovascular events by
14%.

The combined results of 14 RCTs investigating statins also found that
a reduction in LDL-cholesterol of 1mmol/L, sustained over a period of 5
years, reduced major vascular events by 23% (Cholesterol Treatment
Trialists' Collaborators, 2005). Chan et al (2011) conducted a meta-
analysis of seven trials investigating the effect of intensive lipid
lowering using statins. The intensive lipid lowering arm had reduced LDL
levels and significantly lower risks for stroke, coronary events, and CVD
and CHD deaths.

The UK National Diet and Nutrition Survey (NDNS) rolling programme
2008/2009 - 2011/2012 shows that people in all age/sex groups are still,
on average, consuming saturated fat above recommendations (12.6% of food
energy for adults aged 19-64 years). The headlines in the press about the
review by Harcombe et al, are likely to have had the damaging effect of
confusing the public about how to choose a healthy diet. Based on the
totality of the evidence, Public Health England will continue to advise
people to consume a diet that is low in saturated fat and support the
Department of Health's Responsibility Deal incentives to reduce saturated
fat in foods.

In addition to focusing on reducing saturated fats, Public Health
England continues to advise that we need to eat fewer calories, less salt
and sugar and more dietary fibre, fruit and vegetables and oily fish.

National Diet and Nutrition Survey: Results from Years 1-4
(combined) of the Rolling Programme (2008/2009 - 2011/12)
www.gov.uk/government/uploads/system/uploads/attachment_data/file/310997/NDNS_Y1_to_4_UK_report_Executive_summary.pdf

Conflict of Interest:

Re: Harcombe et al. Evidence from randomised controlled trials did
not support the introduction of dietary fat guidelines in 1977 and 1983:

The claim made by the authors of this paper that guidelines on
dietary fat introduced in the 1970s and 1980s were not based on good
scientific evidence is misguided and potentially dangerous. Whilst it is
important to ensure an ongoing interrogation of the evidence linking d...

Re: Harcombe et al. Evidence from randomised controlled trials did
not support the introduction of dietary fat guidelines in 1977 and 1983:

The claim made by the authors of this paper that guidelines on
dietary fat introduced in the 1970s and 1980s were not based on good
scientific evidence is misguided and potentially dangerous. Whilst it is
important to ensure an ongoing interrogation of the evidence linking diet
and heart disease, this must be through an holistic assessment of the
evidence base and recognition of the clear improvements in population
cholesterol levels and heart health that have taken place over the past 40
years.

In their assessment of the meta-analysis of randomised controlled
trial (RCT) data for saturated fat intake and heart disease mortality,
Harcombe et al.1 have taken a classical pharmaceutical approach to the
evidence, with the assumption that as with drugs, RCTs provide the gold
standard for formulating public health guidelines on diet. The assumption
that RCTs represent the pinnacle of the evidential hierarchy against which
other types of study compare unfavourably has been repeatedly shown to be
unproven for diet. In fact such an approach would be inappropriate for
most population based recommendations (as was also argued in the
accompanying editorial by Bahl 2).

Most dietary guidelines have been developed using an approach to risk
assessment which is based on assessing the degree of consistency and
quality of the data from a number of different types of studies;
convergence of the evidence represents the gold standard for risk
assessment in the study of diet-disease relationships. This approach uses
RCT data where it is available and with due caution for the extrapolation
of the findings to healthy populations, since many are conducted in high
risk individuals or those with existing disease. At the time of the
introduction of the UK and US guidelines, consistent evidence for
cholesterol raising effects of saturated fats was available from animal
studies, cross country comparisons, retrospective case control and
prospective cohort studies. The RCT studies discussed by Harcombe et al 1
were available to the expert committees at the time the guidelines were
drawn up. These findings were in part responsible for the decisions not to
recommend complete replacement of dietary saturated fats with
polyunsaturated fats, due to possible adverse effects of higher intakes of
these fats. At the time the recommendations were made evidence was also
available from trials conducted in metabolic ward and semi-free-living
settings in volunteer subjects. These showed effects of saturated fats on
circulating cholesterol to be so consistent that investigators were able
to develop predictive algorithms which would estimate the cholesterol
outcome based on the fat composition of the diet being fed.3

The discovery of the LDL receptor in the 1970s 4 paved the way to a
molecular based understanding of the mechanisms by which different dietary
fatty acids influence the hepatic uptake and excretion of circulating LDL
and thereby circulating LDL cholesterol concentrations. So a feasible
molecular mechanism was beginning to emerge which subsequently powerfully
supported the epidemiological and experimental studies.

In support of their own findings Harcombe et al.1 highlight the
recent meta-analyses of the cohort data 5, 6 which has argued that more
recent cohort studies have shown lower relative risk ratios for saturated
fat than earlier studies. Within these analyses it is astonishing to note
the limited attention given to the changes that have taken place in
population diets over the past 40 years, since this is a potentially
powerful confounding factor in long term cohort studies. Since the 1960s,
dietary fat intake in the UK has fallen by 50% -from around 125g/d to less
than 83g/d today. Saturated fat intakes have fallen even more dramatically
- from around 55g/d to around 30g/d today, with most of this change
occurring between 1975 and 1995.7,8 For the cohorts which were initiated
in the 1960s and 1970s the baseline diet measured at the outset of the
study bears little resemblance to the diet the subjects would have been
eating during the subsequent follow up periods. Those few cohort studies
which have undertaken repeat diet assessments have confirmed that the risk
ratio has reduced as population diet has changed, thereby providing real
life evidence of the benefits of the recommended diet. Exactly similar
changes are seen for trans fats; where repeat dietary assessment data are
available within cohort studies the risk ratio for the population study
group has fallen as levels of trans fats in the background diet has
reduced. In the Nurses Health Study after an 8 year follow up the odds
ratio fell from 1.67 reported in 1993 9 to 1.53 in 1997 10 and to 1.33 in
2005 11. It is intriguing to note the concerns regarding recommendations
for saturated fats have not been raised for trans fatty acids despite
exactly similar 'limitations' concerning the types and quality of evidence
available. There are no RCTs of coronary mortality available for trans
fatty acids, with lipoprotein biomarker outcomes used to support reduction
in intakes of these fats.

As far as more recent studies are concerned, those established since
1995 demonstrate a much narrower range of saturated fat intakes than was
the case in the 1960s and 1970s. The lower risk ratios reflect the fact
that significant proportion of the study cohorts are now eating levels of
saturated fats that do not elevate LDL cholesterol and lead to risk of
heart disease. It should be expected that outcomes from studies conducted
since 1995 will be less likely to observe significant effects of either
trans or saturated fat on heart disease, precisely because the recommended
diets have been beneficial to population heart health. Given the
improvements in both levels of cholesterol and rates of heart disease
world-wide in those countries which have introduced measures to reduce
intakes of saturated fats, it would seem that an RCT, with corresponding
ethical approval for its conduct, would surely be required to reverse
existing recommendations?

REFERENCES

1. Harcombe Z, Baker JS, Cooper SM, et al. Evidence from randomised
controlled trials did not support the introduction of dietary fat
guidelines in 1977 and 1983: a systematic review and meta-analysis. Open
Heart 2015;2:e000196.

We are currently finalising the follow-up paper, which is to consider
all RCT evidence for current dietary guidelines before and since their
introduction, to see if they have been supported in hindsight. We will
review the risk of bias assessment tool, as suggested.

We do accept the role that cohort studies can play but wanted to
focu...

We are currently finalising the follow-up paper, which is to consider
all RCT evidence for current dietary guidelines before and since their
introduction, to see if they have been supported in hindsight. We will
review the risk of bias assessment tool, as suggested.

We do accept the role that cohort studies can play but wanted to
focus on RCTs to ask if this evidence alone supported the introduced
dietary guidelines. One of the authors, ZH, is undertaking a PhD on the
topic of the evidence base for dietary fat guidelines and is reviewing RCT
and cohort evidence before and after the recommendations were introduced.

The Sydney heart study was excluded for sensitivity analysis and the
results remained non-significant. The process was repeated with the
exclusion of each study individually and no combination of remaining RCTs
could establish a significant result.

We commented on the weight data in the discussion: "Studies of the
time report weight, not body mass. Weight changes were not recorded in two
studies[1 2]. Two studies noted no significant weight change in
intervention or control groups[3 4]. The Research Committee study[5]
reported mean weight loss as 7.5% in the intervention group and 4.8% in
the control group. Woodhill et al[6] reported a mean weight loss of 6.5%
and 6.0% in the intervention and control groups respectively." The weight
information available did not serve as an explanation for differences in
cholesterol levels.

We stand by our conclusion that, having reviewed evidence available
to the committees, the guidelines should not have been introduced.

4. Medical Research Council. Controlled trial of soya-bean oil in
myocardial infarction: Report of a research committee to the Medical
Research Council. The Lancet 1968;292(7570):693-700 doi:
http://dx.doi.org/10.1016/S0140-6736(68)90746-0[published Online First:
Epub Date]|.